Roles of histidine charge and cardiolipin in membrane disruption by antimicrobial peptides Gaduscidin-1 and Gaduscidin-2.

Gad-1 and Gad-2 are helical, histidine-rich antimicrobial peptides (AMPs) from paralogous genes in cod. 15N and 2H solid state nuclear magnetic resonance (NMR) were used to characterize their lipid-bound structures and lipid interactions. Gad-1 was found to position in-plane in POPC: POPG bilayers. Gad-1 displayed greater effects than Gad-2 on lipid acyl chain order of POPE: POPG and POPE: POPG: CL bilayers, in keeping with its greater activity against E. coli. The effect of Gad-1 and Gad-2 on lipid bilayer order was only weakly affected by changes in pH, and hence changes in histidine charge. This was somewhat surprising for Gad-2 as this peptide's biological activity has been shown to be greater at low pH and thus the finding may point to the existence of functional interactions with non-lipid components of bacteria. The incorporation of cardiolipin into POPE: POPG bilayers in such a way as to preserve the overall charge of the bilayers did not alter Gad-1's effects on lipid acyl chain order parameters, which report on motions on the 10-5 s timescale. When cardiolipin and Gad-1 were both present, there were subtle changes on membrane dynamics at other timescales.

Role of Charge in Lipid Vesicle Binding and Vesicle Surface Saturation by Gaduscidin-1 and Gaduscidin-2.

The histidine-rich antimicrobial peptides Gad-1 and Gad-2, from paralogous genes in cod, provide an opportunity to examine the effect of charge and nonelectrostatic factors on peptide-vesicle interaction and on peptide antimicrobial activity. In this study, the dependence of vesicle ζ-potential on peptide concentration has been used to examine the binding of these peptides to model vesicle surfaces at pH = 5.0, for which the charges of Gad-1 and Gad-2 are +8 and +5, respectively, and at pH = 7.0, where their charges are +3 and +1, respectively. Interpreting the observed ζ-potential behaviors as examples of Langmuir adsorption isotherms, it is possible to infer the equilibrium constant for peptide-vesicle binding, the fraction of the peptide bound at low peptide concentration, and the maximum peptide-to-lipid ratio when the vesicle surface is saturated at high peptide concentration. For both peptides, higher peptide charge is found to be correlated with a lower fraction of the peptide being bound to vesicle surfaces at low peptide concentration and with a smaller maximum bound peptide-to-lipid ratio at high peptide concentration. The equilibrium binding constant, on the other hand, is more strongly correlated with the peptide sequence than with the charge. Gad-1, which has been shown to be more biologically active than Gad-2, displayed a significantly higher equilibrium binding constant. These observations suggest that while the maximum peptide density on the vesicle surface is limited by electrostatic interactions, the free energy of peptide binding, like the observed antimicrobial activities of the Gad peptides, is also sensitive to other peptide factors which might, for example, influence hydrophobic interactions.

Risk and protective factors associated with the mental health of young adults in Kabul, Afghanistan.

BACKGROUND: We examined the mental health status and severity of psychological distress symptoms among young adults residing in Kabul, Afghanistan and determined how such outcomes might be influenced by an array of risk and protective factors. METHODS: A cross-sectional study design was adopted using convenience, snowball, and street-intercept recruitment techniques. Surveys were completed by 232 young adults between 18 and 35 years of age in September 2015. We used both etic (mental health component of the SF-8) and emic (Afghan Symptom Checklist) measures of mental health and psychological distress, respectively, and regressed these outcome measures against socio-demographic, physical health, and psychological variables (resilience, hope-optimism) using ordinary least squares (OLS) regression methods. RESULTS: We found that poor mental health is common in this sample, affecting 75% of participants; and, that distress symptoms (depressive, anxiety, and somatoform symptoms) occur often. Regression models were consistent in showing higher education as a risk-factor for both outcomes, whereas, age, ethnicity, and income significantly contributed only to the ASCL model as risk-factors. However, both outcomes were strongly influenced by protective factors such as good physical health status and higher perceived hope-optimism. CONCLUSIONS: Our study provides further evidence of how current economic conditions in Kabul contribute to poor mental health and symptom severity, but also show how positive physical health and perceived hope-optimism can be protective. This study provides support for developing culturally-competent policies and interventions that build on protective factors.

Conflicts in operating room: Focus on causes and resolution.

The operation theater (OT) environment is the most complex and volatile workplace where two coequal physicians share responsibility of one patient. Difference in information, opinion, values, experience and interests between a surgeon and anesthesiologist may arise while working in high-pressure environments like OT, which may trigger conflict. Quality of patient care depends on effective teamwork for which multidisciplinary communication is an essential part. Troubled relationships leads to conflicts and conflicts leads to stressful work environment which hinders the safe discharge of patient care. Unresolved conflicts can harm the relationship but when handled in a positive way it provides an opportunity for growth and ultimately strengthening the bond between two people. By learning the skills to resolve conflict, we can keep our professional relationship healthy and strong which is an important component of good patient care.

Comparative evaluation of oral flupirtine and oral diclofenac sodium for analgesia and adverse effects in elective abdominal surgeries.

BACKGROUND: Flupirtine is a centrally-acting, nonopioid analgesic that interacts with N-methyl-D-aspartate receptors. AIM: The present study was designed to compare analgesic efficacy and adverse effects of orally administered flupirtine and diclofenac sodium for postoperative pain relief. SETTINGS AND DESIGN: In a prospective, randomized double-blind study, 100 patients of American Society of Anesthesiologist grade I and II in the age group of 18-65 years of either sex undergoing elective abdominal surgeries were included after taking informed consent. MATERIALS AND METHODS: The present study started after 12 h of surgery and patients were randomly divided into two groups of 50 each. For postoperative analgesia, group A received flupirtine 100 mg orally and group B received diclofenac sodium 50 mg orally and study drugs were repeated every 6 hourly for 5 days postoperatively. Vital parameters and visual analogue scale (VAS) scores for pain were recorded at 0, 1, 2, 4, 6, 8, 12, 16 and 24 h, and adverse effects were noted for 48 h of the study period. STATISTICAL ANALYSIS: Data were compiled and analyzed statistically using Chi-square test and two-tailed Student's t-test. RESULTS: Visual analogue scores decreased more rapidly in diclofenac group during 1(st) h, hence there was rapid onset of analgesia in this group as compared to flupirtine group but later on VAS was comparable in both groups at all measured intervals (P > 0.05). Patients in diclofenac group experienced significantly more heartburn (P = 0.00), impaired taste sensation (P < 0.001) and dizziness (P = 0.004) as compared to flupirtine group. CONCLUSION: Oral flupirtine and diclofenac sodium were equally effective for postoperative analgesia. There was faster onset of analgesia with diclofenac sodium, but flupirtine was better tolerated by the patients because of its minimal adverse effects.

Incidence, mortality, and racial differences in peripartum cardiomyopathy.

There are no large population-based studies on the incidence and prognosis of peripartum cardiomyopathy (PC). Between 1996 and 2005, there were 241,497 deliveries within the Southern California Kaiser healthcare system. Among these, we identified 60 cases of PC by searching for an International Classification of Diseases, Ninth Edition diagnosis of heart failure (HF) and detailed chart review. PC was confirmed if all of the following criteria were satisfied: (1) left ventricular ejection fraction <0.50, (2) met the Framingham criteria for HF, (3) new symptoms of HF or initial echocardiographic diagnosis of left ventricular dysfunction occurred in the month before or in the 5 months after delivery, and (4) no alternative cause of HF could be identified. The overall incidence of PC was 1 in 4,025 deliveries. The incidence in whites, African-Americans, Hispanics, and Asians was 1 of 4,075, 1 of 1,421, 1 of 9,861, and 1 of 2,675 deliveries, respectively. The incidence of PC was greatest in African-Americans, which was 2.9-fold higher compared with whites (p = 0.03) and 7-fold that of Hispanics (p <0.001). With a mean follow-up of 4.7 years, the freedom from all-cause death was 96.7% by the Kaplan-Meier method. In conclusion, this large population-based study highlights important racial differences in the incidence of PC. We observed the lowest incidence of PC in Hispanics and the highest in African-Americans. Our findings also suggest that the current mortality associated with PC may be less than reported in older series, perhaps because of the high utilization of modern HF therapy.